Phase 2 LX-101 IGF-1R–targeted methotrexate conjugate in R/R Ewing sarcoma/DSRCT

MD Anderson’s RAPID platform is an open-label, Bayesian, multi-center Phase 2 study designed to quickly screen “promising drugs” and combinations for adolescent and young adult patients with relapsed/refractory Ewing sarcoma (ES), desmoplastic small round cell tumor (DSRCT), and related small round cell sarcomas (SRCS), typically in the third-line-and-beyond setting. One investigational arm evaluates LX-101, a targeted cytotoxic conjugate that uses an IGF-1 variant to bind insulin-like growth factor 1 receptor (IGF-1R) and deliver a methotrexate payload (a folate antagonist that blocks DNA synthesis), aiming to concentrate chemotherapy-like effect in IGF-1R–driven tumors. LX-101 is being developed by Lirum Therapeutics, while the platform is investigator-initiated and sponsored by The University of Texas MD Anderson Cancer Center. The scientific bet is that IGF pathway dependence in ES and DSRCT can be exploited with a targeted “payload-bearing” approach rather than non-specific chemotherapy. Today, patients with R/R ES or DSRCT commonly cycle through salvage multi-agent chemotherapy regimens and clinical trials, with limited durable benefit once disease is refractory.